The overall goal of our laboratory is a richer understanding of the structural and physiological bases of the frequency selectivity or tuning in the vertebrate auditory system. Driven by a knowledge of the animal's acoustic behavior in its natural habitat, our primary objectives for the proposed research are threefold: (1) to apply modern techniques to provide new insights into the physiological and biophysical mechanisms underlying the localization of airborne sound and substrate-borne vibration in the vertebrate ear, (2) to gain an understanding and appreciation of the mechanisms underlying the electrical and mechanical cellular processes that modulate and sculpt low-frequency selectivity in the auditory periphery, and (3) to explore the physiological bases underlying the newly-discovered remarkable ultrasonic sensitivity in the amphibian ear. To accomplish these objectives, a series of four detailed investigations will be performed in order to (a) directly measure the motion of the middle ear ossicles in a "low-frequency" animal, the golden mole, in order to characterize the directional responses of the middle ear ossicles to airborne and seismic stimuli- and thus extend our observations to a subterranean seismic specialist, (b) systematically compare both receptor pharmacology and ionic current kinetics in the same hair cell preparation to directly test the effects of exogenous agents on tuning properties of low-frequency hair cells, (c) examine the calcium-calmodulin- dependent contractile mechanism mediating slow motility in response to extracellular stimuli in vertebrate hair cells, and (d) characterize the tuning of the peripheral auditory system of a high-frequency specialist and to determine the mechanisms subserving this tuning. The data that result will be rich in implications regarding the processing of airborne sound and substrate vibration as well as the role of efferent-mediated feedback in frequency tuning. Thus, this work is expected to provide a framework for understanding both airborne and bone-conducted sound transmission and tuning in animals, including humans. Of major current interest is the putative role of the efferent system in the genesis of frequency selectivity and protection against noise overstimulation. Ultimately, our research may lead to new therapeutic approaches to treatment of hyperacusis and noise-induced tinnitus, two known syndromes in which efferent system malfunction has been implicated. [unreadable] [unreadable] [unreadable]